比较子宫内暴露于齐多夫定或替诺福韦的新生儿脐带血细胞中的基因毒性特征。
Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.
作者信息
Vivanti Alexandre, Soheili Tayebeh S, Cuccuini Wendy, Luce Sonia, Mandelbrot Laurent, Lechenadec Jerome, Cordier Anne-Gael, Azria Elie, Soulier Jean, Cavazzana Marina, Blanche Stéphane, André-Schmutz Isabelle
机构信息
aInstitut National de la Santé et de la Recherche Médicale (INSERM), U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine bLaboratoire d'Hématologie Biologique, Assistance Publique-Hopitaux de Paris (AP-HP) cLaboratoire Génome et Cancer, INSERM, U944 and UMR7212, Hôpital Saint Louis dService de Gynécologie Obstétrique, Hôpital Louis Mourier, Hôpitaux Universitaire Paris Nord Val de Seine (HUPNVS), AP-HP, Colombes eINSERM U1018, Centre de recherche en Epidémiologie et Santé des Populations fUniversité Paris-Sud, Le Kremlin Bicêtre gService de Gynécologie Obstétrique, Hôpital Antoine Béclère, AP-HP, Clamart hService de Gynécologie Obstétrique, Hôpital Bichat, HUPNVS, AP-HP iUniversité Paris-Diderot jInstitut Universitaire d'Hématologie, Paris kDépartement de Biothérapie lUnité d'Immunologie Hématologie Rhumatologie Pédiatrique, Hôpital Necker Enfants Malades, AP-HP mEA 7323, Pharmacologie et évaluation des médicaments chez l'enfant et la femme enceinte, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. *Stéphane Blanche and Isabelle André-Schmutz contributed equally to the writing of this article.
出版信息
AIDS. 2015 Jul 17;29(11):1319-24. doi: 10.1097/QAD.0000000000000564.
OBJECTIVES
Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero.
DESIGN
We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively).
METHODS
The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs.
RESULTS
Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups.
CONCLUSION
Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes.
目的
齐多夫定和替诺福韦是用于预防母婴传播HIV的两种主要核苷（酸）类似物。在体外，这两种药物均可与人类DNA结合并整合其中，抑制端粒酶。本研究的目的是评估基于齐多夫定或替诺福韦的联合疗法对子宫内暴露的新生儿脐带血细胞的遗传毒性作用。
设计
我们比较了孕期暴露于基于齐多夫定或替诺福韦联合疗法的新生儿脐带血样本以及未暴露对照组（分别为n = 8、9和8）的非整倍体率和基因表达谱。
方法
通过脐带血T细胞核型测定非整倍体率。用微阵列确定脐带血T细胞以及造血干细胞和祖细胞的基因表达谱，在基因集富集分析中进行分析，并通过实时定量PCR进行验证。
结果
齐多夫定暴露组的非整倍体发生率（26.3%）高于替诺福韦暴露组（14.2%）或对照组（13.3%；两者P均<0.05）。在齐多夫定和替诺福韦暴露组的样本中，参与DNA修复、端粒维持、核苷酸代谢、DNA/RNA合成和细胞周期的基因转录均失调。
结论
尽管替诺福韦的致断裂作用低于齐多夫定，但基因表达谱分析显示，两种药物均会改变DNA修复和端粒维持基因的转录。
Zotero 插件